Immunoglobulin Fold: Structures of Proteins in the Immunoglobulin Superfamily

Abstract

Proteins of the immunoglobulin fold are built of homologous domains of approximately 100 residues and with a structure formed by two β sheets packed face to face. Functions of the proteins are mainly in the immune system, cell–cell recognition or in the structural organization and regulation of muscle.

Keywords: immunoglobulin structures; gene structures; structural determinants; binding sites

Figure 1.

The domain structure of some members of the immunoglobulin superfamily. The domain structure is shown for the neural cell adhesion molecule (NCAM), the CD2 adhesion molecule, an antibody and a small fragment of the muscle protein titan. The immunoglobulin superfamily domains are shown as ovals, consist of about 100 residues and belong to one of four structural sets I, V, C1 or C2 (see text). NCAM and titan also have fibronectin type III domains (FnIII), shown as squares.

Figure 2.

The secondary structure commonly found in I set domains. It mainly consists of two twisted β sheets packed face to face. The β‐sheet strands are represented by thick ribbons. One β sheet has five strands, A′, G, F, C and C′, and the other has four, A, B, E and D. The EF turn has one turn of α helix.

Figure 3.

The β‐sheet structures commonly found in the (a) I, (b) C1, (c) V and (d) C2 sets of the immunoglobulin superfamily. Closed circles represent β‐sheet residues; open circles represent residues in loops that have conserved conformations, and horizontal broken lines represent hydrogen bonds. To help compare the structures of the different sets we indicate the positions of the Cys residues (⋄) that are strongly conserved in the V and C1 sets but less conserved in the I and C2 sets.

Figure 4.

The gene structure of the part of the chicken neural cell adhesion molecule (NCAM) gene that codes for the extracellular domains. Note that the exon (broad line) and intron (narrow line) regions are not drawn to scale; 0, 1 and 2 are intron phases. This region of the gene codes for five immunoglobulin superfamily modules or domains (numbered 1 to 5) and two type III fibronectin domains (6 and 7). Forms of the protein found in muscle also contain the small muscle‐specific domain (MSD).

Figure 5.

The hypervariable regions that form the antigen‐binding site of an antibody. The binding site is formed by six polypeptide loops: three from the VL domain, L1, L2 and L3, and three from the VH domain, H1, H2 and H3. These regions join strands of the β‐sheet structure that forms the framework of the variable domains. Four of these link adjacent strands: L2 (strands C′ and C′′), L3 (F and G), H2 (C′ and C′′) and H3 (F and G). The other two, L1 and H1, join strands in different β sheets (strands B and C) (see Figure ).

Figure 6.

The VH locus in (a) humans and (b) chickens (see text).

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References

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Thiebe R, Schäble KF, Bensch A et al. (1999) The variable genes and gene families of the mouse immunoglobulin k locus. European Journal of Immunology 29: 2072–2081.

Further Reading

Galitsky BA, Gelfand IM and Kister AE (1999) Class‐defining characteristics in the mouse heavy chains of variable domains. Protein Engineering 12: 101–107.

Schäble KF, Thiebe R, Bensch A et al. (1999) Characteristics of the immunoglobulin Vk genes, pseudogenes, relics, and orphons in the mouse genome. European Journal of Immunology 29: 2082–2086.

Thiebe R, Schäble KF, Bensch A et al. (1999) The variable genes and gene families of the mouse immunoglobulin k locus. European Journal of Immunology 29: 2072–2081.

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How to Cite close
Gelfand, Israel M, Chothia, Cyrus, and Kister, Alexander E(Apr 2001) Immunoglobulin Fold: Structures of Proteins in the Immunoglobulin Superfamily. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003051]